Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our prior analysis of gene expression in tumor endothelium led to the identification of a G-protein coupled receptor called TEM5. In an attempt to understand the role of TEM5 in angiogenesis and its importance for tumor growth, we previously embarked upon a hunt for its physiological ligand. Through a number of serendipitous events we have now come across what appears to be a ligand for TEM5. We are currently characterizing this factor and its role in tumorigenesis.